Loving Crystal L, Osorio Manuel, Kim Yun-Gi, Nuñez Gabriel, Hughes Molly A, Merkel Tod J
Laboratory of Respiratory and Special Pathogens, Division of Bacterial, Parasitic and Allergenic Products, CBER, FDA, Bethesda, Maryland, USA.
Infect Immun. 2009 Oct;77(10):4529-37. doi: 10.1128/IAI.00563-09. Epub 2009 Jul 20.
Toll-like receptors and Nod-like receptors (NLR) play an important role in sensing invading microorganisms for pathogen clearance and eliciting adaptive immunity for protection against rechallenge. Nod1 and Nod2, members of the NLR family, are capable of detecting bacterial peptidoglycan motifs in the host cytosol for triggering proinflammatory cytokine production. In the current study, we sought to determine if Nod1/Nod2 are involved in sensing Bacillus anthracis infection and eliciting protective immune responses. Using mice deficient in both Nod1 and Nod2 proteins, we showed that Nod1/Nod2 are involved in detecting B. anthracis for production of tumor necrosis factor alpha, interleukin-1 alpha (IL-1 alpha), IL-1 beta, CCL5, IL-6, and KC. Proinflammatory responses were higher when cells were exposed to viable spores than when they were exposed to irradiated spores, indicating that recognition of vegetative bacilli through Nod1/Nod2 is significant. We also identify a critical role for Nod1/Nod2 in priming responses after B. anthracis aerosol exposure, as mice deficient in Nod1/Nod2 were impaired in their ability to mount an anamnestic antibody response and were more susceptible to secondary lethal challenge than wild-type mice.
Toll样受体和Nod样受体（NLR）在感知入侵微生物以清除病原体以及引发适应性免疫以抵御再次攻击方面发挥着重要作用。NLR家族成员Nod1和Nod2能够在宿主细胞质中检测细菌肽聚糖基序，从而触发促炎细胞因子的产生。在本研究中，我们试图确定Nod1/Nod2是否参与感知炭疽芽孢杆菌感染并引发保护性免疫反应。利用缺乏Nod1和Nod2蛋白的小鼠，我们发现Nod1/Nod2参与检测炭疽芽孢杆菌，以产生肿瘤坏死因子α、白细胞介素-1α（IL-1α）、IL-1β、CCL5、IL-6和KC。当细胞暴露于活孢子时，促炎反应比暴露于辐照孢子时更高，这表明通过Nod1/Nod2识别营养型杆菌具有重要意义。我们还确定了Nod1/Nod2在炭疽芽孢杆菌气溶胶暴露后引发反应中的关键作用，因为缺乏Nod1/Nod2的小鼠在产生回忆性抗体反应的能力方面受损，并且比野生型小鼠更容易受到二次致死性攻击。
